2 Cell Adhesion and Biofilm Formation as Target for Therapy The resistance of P. aeruginosa against antibiotics also results from its potential for biofilm formation, in addition to other resistance mechanisms described above. In a biofilm, bacteria are protected against host immune defense and antibiotic treatment. The biofilm development of P. aeruginosa is proposed as a five stage process (Figure 2) based on in vitro observations.38,39 The first step is the reversible attachment of single bacterium to a surface. After a critical local density of bacteria is achieved (irreversible attachment), P. aeruginosa starts to produce an extracellular polymeric substances (EPS) containing matrix (early maturation) which encloses the final mushroom shaped mature biofilm (late maturation). To colonize further regions, the bacteria are then able to disperse from the biofilm in the last stage (dispersion). Notably, biofilms found in vivo are significantly smaller in size and mushroom-shaped structures have not been observed.40